Download Cancer Prone Disease Section Xeroderma pigmentosum Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Cancer Prone Disease Section
Mini Review
Xeroderma pigmentosum
Claude Viguié
Service de Dermatologie, Hôpital Tarnier-Cochin, 89 rue d'Assas, 75006 Paris, France (CV)
Published in Atlas Database: October 2000
Online updated version : http://AtlasGeneticsOncology.org/Kprones/XerodermaID10004.html
DOI: 10.4267/2042/37682
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2000 Atlas of Genetics and Cytogenetics in Oncology and Haematology
C, D, E, F, G and 7 characterized genes). Intensity and
precocity of signs are dependent on the gene involved;
groups A, C, D and G are associated with a more
severe disease.
The same genes are implicated in two related diseases:
Cockayne syndrome (groups B, D and G) and
trichothiodystrophy (groups B and D).
Identity
Inheritance
Recessive autosomal; occurrence is favored by
consanguinity; frequency is 0.3/105 with large
geographical variations; higher frequenciy observed in
Tunisia (10/105, role of consanguinity) and in Japan
(1/105); rare in black people.
Neoplastic risk
Propensity to cutaneous tumors after sun exposure (risk
X 1000 to develop cancer on sun -exposed areas of the
skin): benign lesions, multiple basal cell carcinomas
and spinal carcinomas (occuring in 2 to 40 year old
patients, median age 8 yrs), malignant melanomas
slightly later than carcinomas (risk x 2000 compared to
normal population), rarely other skin tumors
(fibrosarcomas, angiosarcomas).
Propensity to various solid tumors (mainly brain
tumors, x 10 to 20 fold in comparison with general
population).
Treatment
Photoprotection; genetic counseling; treatment of
malignant tumors.
Evolution
Progressively increasing number of cutaneous, ocular
and other solid tumors; cutaneous atrophy with
numerous scars and aesthetic damage; skin
abnormalities comparable to what is clinically and
histologically observed with aging; blindness; severe
mental retardation.
Prognosis
2/3 death before adult age.
Clinics
Note
Xeroderma pigmentosum (XP) is caused by a defect in
nucleotide excision repair mechanisms; various clinical
aspects and intensity of signs are described according
to the gene involved (7 known complement groups) and
type of mutation.
Phenotype and clinics
Severe sun photosensitivity (poikilodermia): induced
precocious cutaneous lesions, concomitant to first sun
exposures, on the exposed areas (hands, arms, face);
dry skin, senile-like, cutaneous retractions (premature
aging of the skin).
Photophobia, often the first sign, before cutaneous
lesions; followed by bilateral cataract; increased risk of
ocular benign and malign tumors.
Neurological signs (14 to 40% of patients): mental
retardation,
pyramidal
syndrome,
peripheral
neuropathia; more severe central nervous system (CNS)
disorders are observed when mutations occur in XPA
DNA binding site.
Clinical heterogeneity: related to genetic heterogeneity
of the disease (7 known complementation groups A, B,
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(4)
226
Xeroderma pigmentosum
Viguié C
Above: characteristic aspect of evolved lesions of the face in an XP patient. To be noted multiple scars of carcinomas and an aged
aspect of the skin with poikilodermia. Below: multiple basocellular carcinomas on the face of an XP patient. Thick arrow points to a recent
lesion, and thin arrow to a scar of an old lesion - Courtesy Daniel Wallach.
complementation groups (XPA to G) plus an additional
variant form, evidenced by somatic cell fusion
experiments.
The genes involved are: XPA, located in 9q22, XPB,
also called ERCC3 (ERCC for Excision-Repair Cross
Complementing rodent repair deficiency), located in
2q21, XPC, located in 3p25, XPD, also called ERCC2,
located in 19q13, XPE, located on chromosome 11
XPF, also called ERCC4, located in 19q13 XPG, also
called ERCC5, located in 13q32, and XPV, also called
Pol eta, and located in 6p12-21.
All XP genes are implicated in various steps of the
NER (nucleotide excision repair) system, except the XP
variant that is mutated in a mutagenic DNA polymerase
(POL H) able to bypass the UV-induced DNA lesions;
various alterations of the same gene may involve
various
phenotypes
Cockayne
syndrome
,
trichothiodystrophy).
Cytogenetics
Inborn conditions
Hypermutability after UV irradiation in cell cultures;
no
increased
of
spontaneous
chromosome
abnormalities in lymphocytes of fribroblastes; however,
after UV-exposure an increased number of sister
chromatid exchanges (SCE) and chromosome
aberrations are observed (mainly chromatid-type
abnormalities); fibroblasts express an increased
sensitivity to chemical mutagens; there is no
cytogenetic feature useful for XP diagnosis.
Genes involved and proteins
Note
The clinical and cytologic XP heterogeneity is the
consequence of the genetic heterogeneity: 7
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(4)
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Xeroderma pigmentosum
Viguié C
Cleaver JE. Common pathways for ultraviolet skin
carcinogenesis in the repair and replication defective groups of
xeroderma pigmentosum. J Dermatol Sci. 2000 May;23(1):1-11
References
Cleaver JE, Thompson LH, Richardson AS, States JC. A
summary of mutations in the UV-sensitive disorders:
xeroderma
pigmentosum,
Cockayne
syndrome,
and
trichothiodystrophy. Hum Mutat. 1999;14(1):9-22
de Boer J, Hoeijmakers JH. Nucleotide excision repair and
human syndromes. Carcinogenesis. 2000 Mar;21(3):453-60
Nakura J, Ye L, Morishima A, Kohara K, Miki T. Helicases and
aging. Cell Mol Life Sci. 2000 May;57(5):716-30
Riou L, Zeng L, Chevallier-Lagente O, Stary A, Nikaido O,
Taïeb A, Weeda G, Mezzina M, Sarasin A. The relative
expression of mutated XPB genes results in xeroderma
pigmentosum/Cockayne's syndrome or trichothiodystrophy
cellular phenotypes. Hum Mol Genet. 1999 Jun;8(6):1125-33
This article should be referenced as such:
Viguié C. Xeroderma pigmentosum. Atlas Genet Cytogenet
Oncol Haematol. 2000; 4(4):226-228.
van Steeg H, Kraemer KH. Xeroderma pigmentosum and the
role of UV-induced DNA damage in skin cancer. Mol Med
Today. 1999 Feb;5(2):86-94
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